title: Characterisation of local immune responses induced by a novel nano-particle based carrier-adjuvant in sheep.
abstract: Most adjuvants require danger signals to promote immune responses against vaccine antigens. Our previous studies have characterised a powerful nano-particulate antigen delivery system, which by itself does not induce inflammation, and which further appears to induce substantial immune responses in mice and sheep without the requirement for added stimulators of toll like receptors or other pathogen recognition receptors. In the present study we dissect the nature of the early induction phase of the immune response stimulated by such a vaccine comprising 40 nm polystyrene nano-particles conjugated to the antigen. We analyse the kinetics of export from an individual draining lymph node from the sheep, of antibodies and cytokines as well as antigen responsive CD4 and CD8 T cells. Our results indicate that simple inert nano-bead based antigen delivery into the draining area of the lymph node is highly efficient at priming combined humoral and T cell antigen specific immunity without the need for added 'danger signals'. Furthermore this nano-bead adjuvant is a potent agent capable of promoting cross-priming for CD8 T cell induction in sheep. Interestingly, using nano-beads, similarly to what has been observed with natural pathogen based lymph node stimulation, a phase of CD4 T cell priming and export preceded CD8 T cell induction, suggesting the engagement of natural priming processes and kinetics.
authors.affiliation: Department of Immunology, Monash University, Victoria 3004, Australia.
authors.forename: Anita
authors.initials: A
authors.lastname: Gamvrellis
authors.forename: Simone
authors.initials: S
authors.lastname: Gloster
authors.forename: Meryem
authors.initials: M
authors.lastname: Jefferies
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Mottram
authors.forename: Peter
authors.initials: P
authors.lastname: Smooker
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
authors.forename: Jean-Pierre Y
authors.initials: JP
authors.lastname: Scheerlinck
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D056724:Immunity, Humoral; D008213:Lymphocyte Activation; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010316:Particle Size; D011137:Polystyrenes; D034561:Sheep, Domestic / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D011137:Polystyrenes; D018074:Vaccines, Conjugate; D010047:Ovalbumin
keywords: Adjuvants; Nano-beads; Ovine; Vaccines